scholarly journals Separated Siamese Twins: Intronic Small Nucleolar RNAs and Matched Host Genes May be Altered in Conjunction or Separately in Multiple Cancer Types

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 387 ◽  
Author(s):  
Marianna Penzo ◽  
Rosanna Clima ◽  
Davide Trerè ◽  
Lorenzo Montanaro
Keyword(s):  
Copy Number ◽  
Host Gene ◽  
The Cancer Genome Atlas ◽  
Cancer Development ◽  
Rna Modification ◽  
Small Nucleolar Rnas ◽  
Multiple Cancer ◽  
Cancer Types ◽  
Nucleolar Rnas ◽  
Host Genes

Small nucleolar RNAs (snoRNAs) are non-coding RNAs involved in RNA modification and processing. Approximately half of the so far identified snoRNA genes map within the intronic regions of host genes, and their expression, as well as the expression of their host genes, is dependent on transcript splicing and maturation. Growing evidence indicates that mutations and/or deregulations that affect snoRNAs, as well as host genes, play a significant role in oncogenesis. Among the possible factors underlying snoRNA/host gene expression deregulation is copy number alteration (CNA). We analyzed the data available in The Cancer Genome Atlas database, relative to CNA and expression of 295 snoRNA/host gene couples in 10 cancer types, to understand whether the genetic or expression alteration of snoRNAs and their matched host genes would have overlapping trends. Our results show that, counterintuitively, copy number and expression alterations of snoRNAs and matched host genes are not necessarily coupled. In addition, some snoRNA/host genes are mutated and overexpressed recurrently in multiple cancer types. Our findings suggest that the differential contribution to cancer development of both snoRNAs and host genes should always be considered, and that snoRNAs and their host genes may contribute to cancer development in conjunction or independently.

scholarly journals Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Étienne Fafard-Couture ◽  
Danny Bergeron ◽  
Sonia Couture ◽  
Sherif Abou-Elela ◽  
Michelle S. Scott
Keyword(s):  
Housekeeping Genes ◽  
Host Gene ◽  
Rna Modification ◽  
Human Tissues ◽  
Rna Seq ◽  
Healthy Human ◽  
Protein Coding ◽  
Conservation Level ◽  
Nucleolar Rnas ◽  
Host Genes

Abstract Background Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions. Results We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver, and brain). We identify 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level, and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. Fifty-nine percent of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, compared to only 16% of the correlated non-coding host gene/snoRNA pairs. Conclusions Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

scholarly journals Higher prevalence of homologous recombination-deficiency in lung squamous carcinoma from African Americans

2019 ◽  
Author(s):  
Sanju Sinha ◽  
Khadijah A. Mitchell ◽  
Adriana Zingone ◽  
Elise Bowman ◽  
Neelam Sinha ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Copy Number ◽  
Squamous Carcinoma ◽  
The Cancer Genome Atlas ◽  
Multiple Cancer ◽  
Homologous Recombination Deficiency ◽  
Molecular Features ◽  
Incidence And Mortality ◽  
Cancer Types ◽  
Lung Squamous Carcinoma

AbstractTo improve our understanding of the longstanding disparities in incidence and mortality across multiple cancer types among minority populations, we performed a systematic comparative analysis of molecular features in tumors from African American (AA) and European American (EA) ancestry. Our pan-cancer analysis on the cancer genome atlas (TCGA) and a more focused analysis of genome-wide somatic copy number profiles integrated with tumor-normal RNA sequencing in a racially balanced cohort of 222 non-small cell lung cancers (NSCLC) reveals more aggressive genomic characteristics of AA tumors. In general, we find AA tumors exhibit higher genomic instability (GI), homologous recombination-deficiency (HRD) levels, and more aggressive molecular features such as chromothripsis across many cancer types, including lung squamous carcinoma (LUSC). GI and HRD levels are strongly correlated across AA tumors, indicating that HRD plays an important role in GI in these patients. The prevalence of germline HRD is higher in AA tumors, suggesting that the somatic differences observed have genetic ancestry origins. Finally, we identify AA-specific copy number-based arm, focal and gene level recurrent features in lung cancer, including a higher frequency of PTEN deletion and KRAS amplification and a lower frequency of CDKN2A deletion. These results highlight the importance of including minority and under-represented populations in genomics research and may have therapeutic implications.

scholarly journals Pan-cancer driver copy number alterations identified by joint expression/CNA data analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gaojianyong Wang ◽  
Dimitris Anastassiou
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Multiple Cancer ◽  
Cancer Driver ◽  
Large Gene ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer

Abstract Analysis of large gene expression datasets from biopsies of cancer patients can identify co-expression signatures representing particular biomolecular events in cancer. Some of these signatures involve genomically co-localized genes resulting from the presence of copy number alterations (CNAs), for which analysis of the expression of the underlying genes provides valuable information about their combined role as oncogenes or tumor suppressor genes. Here we focus on the discovery and interpretation of such signatures that are present in multiple cancer types due to driver amplifications and deletions in particular regions of the genome after doing a comprehensive analysis combining both gene expression and CNA data from The Cancer Genome Atlas.

scholarly journals Are spliced ncRNA host genes distinct classes of lncRNAs?

2020 ◽  
Vol 139 (4) ◽  
pp. 349-359
Author(s):  
Rituparno Sen ◽  
Jörg Fallmann ◽  
Maria Emília M. T. Walter ◽  
Peter F. Stadler
Keyword(s):  
Gene Function ◽  
Negative Answer ◽  
Positive Answer ◽  
Host Gene ◽  
Small Nucleolar Rnas ◽  
Biological Functions ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractMany small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless, there is mounting evidence that the host genes have biological functions beyond their primary task of carrying a ncRNA as payload. So far, no connections between the function of the host genes and the function of their payloads have been reported. Here we investigate whether there is evidence for an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNA host genes can be distinguished based on sequence and/or structure features unrelated to their payload. A positive answer would imply a functional and mechanistic correlation between host genes and their payload, provided the classification does not depend on the presence and type of the payload. A negative answer would indicate that to the extent that secondary functions are acquired, they are not strongly constrained by the prior, primary function of the payload. We find that the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads. They become virtually indistinguishable, however, as soon as only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. This indicates that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.

scholarly journals Dynamics and modulation of the human snoRNome

2021 ◽  
Author(s):  
Étienne Fafard-Couture ◽  
Danny Bergeron ◽  
Sonia Couture ◽  
Sherif Abou Elela ◽  
Michelle S Scott
Keyword(s):  
Expression Patterns ◽  
Housekeeping Genes ◽  
Host Gene ◽  
Rna Modification ◽  
Human Tissues ◽  
Healthy Human ◽  
Protein Coding ◽  
Conservation Level ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractBackgroundSmall nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA expression patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions.ResultsWe used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver and brain). We identified 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. 59% of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, as opposed to only 16% of the correlated non-coding host gene/snoRNA pairs.ConclusionsOur results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.

scholarly journals Identification and Characterization of MicroRNAs Associated with Somatic Copy Number Alterations in Cancer

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 475 ◽  
Author(s):  
Jihee Soh ◽  
Hyejin Cho ◽  
Chan-Hun Choi ◽  
Hyunju Lee
Keyword(s):  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Cancer Development ◽  
Cancer Type ◽  
Biological Processes ◽  
Copy Number Alterations ◽  
Coding Regions ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Somatic Copy Number Alterations

MicroRNAs (miRNAs) are key molecules that regulate biological processes such as cell proliferation, differentiation, and apoptosis in cancer. Somatic copy number alterations (SCNAs) are common genetic mutations that play essential roles in cancer development. Here, we investigated the association between miRNAs and SCNAs in cancer. We collected 2538 tumor samples for seven cancer types from The Cancer Genome Atlas. We found that 32−84% of miRNAs are in SCNA regions, with the rate depending on the cancer type. In these regions, we identified 80 SCNA-miRNAs whose expression was mainly associated with SCNAs in at least one cancer type and showed that these SCNA-miRNAs are related to cancer by survival analysis and literature searching. We also identified 58 SCNA-miRNAs common in the seven cancer types (CC-SCNA-miRNAs) and showed that these CC-SCNA-miRNAs are more likely to be related with protein and gene expression than other miRNAs. Furthermore, we experimentally validated the oncogenic role of miR-589. In conclusion, our results suggest that SCNA-miRNAs significantly alter biological processes related to cancer development, confirming the importance of SCNAs in non-coding regions in cancer.

scholarly journals Computing MicroRNA-Gene Interaction Networks in Pan-cancer Using MiRDriver

2021 ◽  
Author(s):  
Banabithi Bose ◽  
Matthew Moravec ◽  
Serdar Bozdag
Keyword(s):  
Copy Number ◽  
Target Genes ◽  
The Cancer Genome Atlas ◽  
Gene Interactions ◽  
Microrna Target ◽  
Multiple Cancer ◽  
Driver Genes ◽  
Microrna Gene ◽  
Cancer Types ◽  
Pan Cancer

Abstract DNA copy number aberrated regions in cancer are known to harbor cancer driver genes and the short non-coding RNA molecules, i.e., microRNAs. In this study, we integrated the multi-omics datasets such as copy number aberration, DNA methylation, gene and microRNA expression to identify the signature microRNA-gene associations from frequently aberrated DNA regions across pan-cancer utilizing a LASSO-based regression approach. We studied 7,294 patient samples associated with eighteen different cancer types from The Cancer Genome Atlas (TCGA) database and identified several cancer-specific microRNA-gene interactions enriched in experimentally validated microRNA-target databases. We highlighted several oncogenic and tumor suppressor microRNAs and genes that were common in several cancer types. Our method substantially outperformed the five state-of-art methods in selecting significantly known microRNA-gene interactions in multiple cancer types. Several microRNAs and genes were found to be associated with tumor survival and progression. Selected target genes were found to be significantly enriched in cancer-related pathways, cancer Hallmark and Gene Ontology (GO) terms. Furthermore, subtype-specific potential gene signatures were discovered in multiple cancer types.

scholarly journals Supervised and Unsupervised Classification of lncRNA Subtypes

2020 ◽  
Author(s):  
Rituparno Sen ◽  
Jörg Fallmann ◽  
Maria Emília M. T. Walter ◽  
Peter F. Stadler
Keyword(s):  
Unsupervised Classification ◽  
Positive Answer ◽  
Host Gene ◽  
Small Nucleolar Rnas ◽  
Biological Functions ◽  
Protein Coding ◽  
Non Coding Rnas ◽  
Nucleolar Rnas ◽  
Host Genes

AbstractMany small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding (lncRNA) host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless there is mounting evidence that the host genes have biological functions. No obvious connections between the function of the host genes and the function of their payloads have been reported. Here we inverstigate whether there is an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNAs host genes can be distinguished based on sequence and structure features. A positive answer would imply a correlation between host genes and their payload. While the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads, this is no longer the case when only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. Our data indicate that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.

scholarly journals Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas

2021 ◽  
Vol 11 ◽  
Author(s):  
Luuk Harbers ◽  
Federico Agostini ◽  
Marcin Nicos ◽  
Dimitri Poddighe ◽  
Magda Bienko ◽  
...  
Keyword(s):  
Copy Number ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Multiple Cancer ◽  
Human Cancers ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Somatic Copy Number Alterations ◽  
Genome Atlas

Somatic copy number alterations (SCNAs) are a pervasive trait of human cancers that contributes to tumorigenesis by affecting the dosage of multiple genes at the same time. In the past decade, The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) initiatives have generated and made publicly available SCNA genomic profiles from thousands of tumor samples across multiple cancer types. Here, we present a comprehensive analysis of 853,218 SCNAs across 10,729 tumor samples belonging to 32 cancer types using TCGA data. We then discuss current models for how SCNAs likely arise during carcinogenesis and how genomic SCNA profiles can inform clinical practice. Lastly, we highlight open questions in the field of cancer-associated SCNAs.

scholarly journals RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival

2022 ◽  
Vol 23 (1) ◽  
pp. 496
Author(s):  
Kenzui Taniue ◽  
Tanzina Tanu ◽  
Yuki Shimoura ◽  
Shuhei Mitsutomi ◽  
Han Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
The Cancer Genome Atlas ◽  
Multiple Cancer ◽  
Pancreatic Cancer Cells ◽  
Cancer Cell Survival ◽  
Cellular Machinery ◽  
Cancer Types ◽  
Rna Exosome ◽  
Tumor Types

The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies’ datasets. We discovered that the EXOSC4 gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that EXOSC4 alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed BIK expression and destabilized SESN2 mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of BIK and SESN2 mRNA in the survival of pancreatic tumor cells.

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